U.S. patent number 4,877,501 [Application Number 07/011,838] was granted by the patent office on 1989-10-31 for process for fabrication of lipid microstructures.
Invention is credited to Jacque H. Georger, Ronald Price, Joel M. Schnur, Paul Schoen, Alok Singh, Paul Yager.
United States Patent |
4,877,501 |
Schnur , et al. |
October 31, 1989 |
Process for fabrication of lipid microstructures
Abstract
Method and process for forming selected microstructures having
predetermined shape and dimension from surfactants comprising the
steps of: selecting a lipid which self aggregates into a
predetermined microstructure selected from the group of helices and
tubules; selecting a lipid solvating organic solvent; dissolving
the selected lipid in the selected organic solvent; adding a
predetermined amount of non-solvent to the selected organic
solvent; and allowing the solution to sit for a predetermined
period of time at a predetermined temperature.
Inventors: |
Schnur; Joel M. (Burke, VA),
Price; Ronald (Grasonville, MD), Yager; Paul
(Washington, DC), Schoen; Paul (Alexandria, VA), Georger;
Jacque H. (Springfield, VA), Singh; Alok (Alexandria,
VA) |
Family
ID: |
21752191 |
Appl.
No.: |
07/011,838 |
Filed: |
February 6, 1987 |
Current U.S.
Class: |
204/157.64;
204/157.73; 204/157.87; 264/4.1; 554/78; 554/84 |
Current CPC
Class: |
B82Y
10/00 (20130101); C11B 3/00 (20130101); C30B
7/00 (20130101); G03F 7/0045 (20130101); G03F
7/025 (20130101); H01L 51/0093 (20130101); C30B
29/58 (20130101) |
Current International
Class: |
C30B
7/00 (20060101); C11B 3/00 (20060101); H01L
51/30 (20060101); G03F 7/025 (20060101); G03F
7/004 (20060101); H01L 51/05 (20060101); B01J
019/08 (); C07F 009/00 (); C11B 003/00 () |
Field of
Search: |
;204/157.15,157.64,157.63,157.67,157.68,157.73,157.87,902
;260/398,398.5,403,405.6,407,410.7,426,428.5 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Yager et al., Mol. Cryst. Liq. Cryst., 1984, vol. 106, 371-381.
.
Yager et al., Biophysical Journal, 1985, vol. 48, 899-906. .
Nakashima et al., J.A.C.S., 1985, vol. 107, 509-510..
|
Primary Examiner: Niebling; John F.
Assistant Examiner: Hsing; Ben C.
Attorney, Agent or Firm: Wolf, Greenfield & Sacks
Government Interests
U.S. GOVERNMENT RIGHTS IN THE INVENTION
This invention was made jointly by three employees of the Naval
Research Laboratory, Washington, D.C. and three employees of
Geo-Centers, Inc. The three Geo-Centers employees, at the time the
invention was made, were in the performance of work under Naval
Research Laboratory contract N00014-85-C-2243. The United States of
America has certain rights in the invention arising out of that
contract, including a nonexclusive, nontransferable, irrevocable,
paid-up license to practice the invention or have it practiced for
or on behalf of the United States throughout the world. The United
States of America may also have rights in the invention derived
form the three employees of the Naval Research Laboratory who are
joint inventors of this invention.
Claims
What is claimed is:
1. Process for forming microstructures of selected shape and
dimension from surfactants comprising the steps of:
selecting a lipid which self aggregates into a microstructure
selected from the group consisting of helices and tubules;
selecting a lipid solvating organic solvent in which
microstructures form;
dissolving the selected lipid in the selected organic solvent;
adding a non-solvent to the selected organic solvent in an amount
sufficient to initiate microstructure growth;
allowing the selected lipid to grow into the microstructure in the
solution of organic solvent and non-solvent for a period of time
and at a temperature below the melting point of the selected
lipid.
2. The process of claim 1 wherein the step of allowing further
comprises maintaining the temperature of the solution at between 10
and about 30 degrees Centigrade below the melting point of the
lipid in water.
3. The process of claim 2 wherein said period of time is less than
about 24 hours.
4. The process of claim 2 wherein the organic solvent is selected
from the group consisting of alcohols, polyols, tetrahydrofuran,
chloroform, and mixtures thereof.
5. The process of claim 2 wherein the step of adding further
comprises adding enough non-solvent to the selected organic solvent
to achieve a volume ratio of organic solvent to non-solvent of
greater than about 1:10.
6. The process of claim 1 wherein said period of time is less than
about 24 hours.
7. The process of claim 1 wherein the organic solvent is selected
from the group consisting of alcohols, polyols, tetrahydrofuran,
chloroform, and mixtures thereof.
8. The process of claim 7 wherein the step of adding further
comprises adding enough non-solvent to the selected organic solvent
to achieve a volume ratio of organic solvent to water of greater
than about 1:10.
9. The process of claim 8 wherein the step of selecting the lipid
further comprises preselecting a certain amount of the lipid to be
dissolved in the selected organic solvent.
10. The process of claim 9 further comprising exposing the lipid
solution for a period of time to radiation which will polymerize
the lipid.
11. The process of claim 9 wherein the selected lipid has the
formula: ##STR3## wherein R.sub.1 and R.sub.2 are selected from the
group consisting of saturated and unsaturated hydrocarbon chains
having fewer than thirty two carbon atoms, X and Y are selected
from the group consisting of alkyl, olefin, and alpha, beta
unsaturated carboxy compounds, and Z is a phosphoryl moiety.
12. The process of claim 11 wherein one of both of R.sub.1 and
R.sub.2 include a diacetylenic moiety in conjugation.
13. The process of claim 12 wherein the non-solvent is selected
from the group consisting of water and hydrocarbon
non-solvents.
14. The process of claim 1 wherein the step of selecting the lipid
further comprises preselecting a certain amount of the lipid to be
dissolved in the selected organic solvent.
15. The process of claim 1 further comprising exposing the lipid
solution for a period of time to radiation which will polymerize
the lipid.
16. The process of claim 1 wherein the selected lipid has the
formula: ##STR4## wherein R.sub.1 and R.sub.2 are selected from the
group consisting of saturated and unsaturated hydrocarbon chains
having fewer than thirty two carbon atoms, X and Y are selected
from the group consisting of alkyl, olefin, and alpha, beta
unsaturated carboxy compounds, and Z is a phosphoryl moiety.
17. The process of claim 16 wherein one or both of R.sub.1 and
R.sub.2 include a diacetylenic moiety in conjugation.
18. The process of claim 17 wherein the non-solvent is selected
from the group consisting of water and hydrocarbon
non-solvents.
19. The process of claim 16 wherein the lipid as the formula:
##STR5## where m and p are selected from the group consisting of 5,
6, 7, 8, 9, 10, and 11 and n and r are selected from the group
consisting of 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16.
Description
BACKGROUND OF THE INVENTION
The present invention relates to the fabrication of lipid
microstructures and in particular to the selective formation of
tubular and helical microstructures of particular handedness from
surfactants. Selected surfactants such as lipids are known to
self-organize into a variety of structures with dimensions on the
micron and submicron scale.
Under typical conditions however, lipids tend to form into a
variety of geometrical forms with little control over dimension and
shape. Heretofore synthetic control over the specific geometrical
form and dimensions of such microstructures has been difficult
except in cases involving lipid vesicles. The present invention
achieves a method for the rational control of the dimensions of
tubular and helical microstructures and the handedness of the
helical microstructures. Such microstructures may be metalized and
are particularly useful in the fabrication of small electrical
circuits.
SUMMARY OF THE INVENTION
In accordance with the invention there is provided a process for
forming selected microstructures having predetermined shape and
dimension from surfactants comprising the steps of: selecting a
lipid which self aggregates into a predetermined microstructure
selected from the group of helices and tubules; selecting a lipid
solvating organic solvent; adding a predetermined amount of water
to the selected organic solvent; allowing the solution to sit for a
predetermined period of time at a predetermined temperature.
The temperature of the formation solution is preferably maintained
at between 10 and about 30 degrees Centigrade below the melting
point as defined in excess water of the selected lipid; and, the
solution is preferably allowed to sit in the shielded environment
for less than about 24 hours.
Most preferably the organic solvent is selected from the group of
alcohols, polyols, tetrahydrofuran, chloroform, and mixtures
thereof and, enough non-solvent such as water (or in the case where
chloroform comprises the selected organic solvent, a hydrocarbon
solvent such as hexane, pentane, heptane, octane or the like) is
added to the selected organic solvent lipid solution to achieve a
volume ratio of organic solvent to non-solvent, preferably water,
of greater than about 1:10. The concentration of the lipid
dissolved in the pre-prepared organic solvent lipid solution is
typically preselected to be less than about 2 mg/ml.
The backbone of the selected surfactant is typically derived from
glycerol.
The lipid is most preferably selected to include one or two
hydrocarbon chains, one or both of which include a diacetylenic
moiety in conjugation within the chains.
The tubular and/or helical microstructures thus formed may be
ruggedized by exposing the selected lipid solution for a
predetermined period of time to high energy radiation which is
capable of polymerizing the lipid.
The present invention most preferably utilizes surfactants having
the following formula I: ##STR1## wherein R.sub.1 and R.sub.2
(attached to a glycerol based backbone) are typically a saturated
or unsaturated hydrocarbon having from about 4 to 32 carbon atoms,
X and Y are typically an alkyl or olefin having fewer than about 16
carbon atoms or an alpha, beta unsaturated carboxy moiety, and Z is
a phosphoryl moiety such as phosphoryl ethanolamine, choline,
serine, inositol, glycerol, 3'-O-aminoacyl glycerol, cardiolipin or
other phosphoryl group found in naturally occurring
phosphoglycerides.
Lipids which are especially capable of rapid formation of the
selected helical and tubular microstructures are those having
hydrocarbon chains such as R.sub.1 and R.sub.2 which contain
diacetylenic moieties, preferably in conjugation. Most preferably
phospholipids having the following formula II are used herein:
##STR2## where m and p are 5, 6, 7, 8, 9, 10, or 11, and n and r
are 0143 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16 and where X, Y and Z
are as mentioned above.
The ready and reproducible formation of tubular and helical
microstructures having a diameter of between about 0.1 and about
3.0 microns, and selected lengths of less than about 1500 microns
is achieved herein. The inventive process herein enables the
formation of tubular and helical microstructures of a particular
handedness formed from the above-referenced surfactants and further
enables the formation of helices (of a selected handedness) and
tubules having preselected lengths and diameters by selective
variation of, inter alia, the composition of solvent in which the
lipids are dispersed, the time of reaction, the temperature of the
reaction mixture, the concentration of lipid in the solution, and
the exposure and/or non-exposure of the reaction mixture to high
energy ionizing (polymerizing) radiation during and after helix
and/or tubule formation.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
A selected surfactant I is preferably first dispersed in a low
molecular weight organic alcohol, polyol, tetrahydrofuran,
chloroform, a mixture of two or more of all of the foregoing or
other suitable water or non-solvent miscible organic solvent.
Suitable organic alcohols and polyols are typically low molecular
weight alcohols and polyols such as methanol, ethanol, propanol,
isopropanol, butanol, isobutanol, propylene glycol, ethylene glycol
and the like. The concentration of the lipid is typically selected
to be less than about 1.5 mg of lipid per ml of organic
solvent.
To the organic solvent lipid mixture is typically next added a
predetermined volume of non-solvent selected to bring the volume
ratio of organic solvent to non-solvent to greater than about 1:10,
typically to between about 5:1 and about 1:5. Water is most
preferred for use as the non-solvent, although other non-solvents
such as hydrocarbons may be utilized in connection with certain
selected lipid solvating organic solvents such as chloroform.
Representative hydrocarbon non-solvents are pentane, hexane,
heptane, octane and the like.
Tubule and helix formation may be effected in an apparently 100%
selected organic solvent, including certain hydrocarbon solvents
such as pentane, hexane, heptane and the like, however, the
inventive method herein typically requires the presence of at least
a trace amount of water.
Upon the addition of water to the organic solvent lipid mixture,
the lipid aggregates into helical or tubular form. The temperature
of the solution is typically maintained at about 10-30 degrees, and
most preferably about 20 degrees Centigrade, below the melting
point of the selected lipid I as defined in excess water. The
helical and tubular aggregates will continue to grow in length from
the lipid over time. According to the invention such tubular
(hollow, open-ended cylinders) and helical (ribbon like--hollow
left handed or right handed helices) lipid aggregates are typically
allowed to grow to selected lengths, in part, by allowing the
formation solution to sit in an environment shielded from radiation
which may polymerize the selected lipid I for a predetermined
period of time, typically less than about 24 hours and preferably
less than about 12 hours.
The right-handedness or left handedness of helices which may be
yielded from certain lipids may be predetermined by selecting a
lipid having a particular chirality with respect to a certain
carbon atom. For example where the preferred lipid I is selected,
the handedness of helical microstructures which may be formed
therefrom may be predetermined by preselecting either the L isomer
(levorotatory) or D isomer (dextrorotatory) with respect to the
central carbon atom of the glycerol based backbone thereof. Where
the L isomer of lipid I is selected, helical microstructures
yielded therefrom will be right-handed only. Where the D isomer is
selected, the helical microstructures will be left-handed only; and
where a racemic mixture of lipid I is used, both left-handed and
right-handed helices will be yielded.
After the lipid mixture is allowed to sit for the preselected
period of time, the tubules and helices thus formed may, if
polymerizable, be ruggedized by polymerization of the lipid. Such
polymerization is typically carried out by subjecting the mixture
to high energy radiation, such as ultraviolet, X-ray, electron
beam, gamma radiation or other radiation which may initiate
polymerization and/or reaction within or between lipid molecules.
Gamma radiation is most preferred to the extent it is less
susceptible to scattering and absorption and thus typically effects
homogenous irradiation. The relatively structurally unstable
tubules and helices formed in the organic solvent, non-solvent
formation solution are structurally locked into (hardened) their
helical or tubular form upon irradiation and thus more readily
retain their hardened structural form for subsequent use in the
fabrication of propellants, resistive elements in small electronic
circuits, separation membranes and the like.
Apart from controlling the extent of growth of the lipid helices
and tubules (i.e. length) by varying the time in which the selected
lipid is allowed to self aggregate in selected solution, the length
of such tubules and helices may also be controlled by preselecting
a relatively specific volume ratio of organic solvent to
non-solvent, preferably water. According to the invention, the
larger the ratio of volume of organic solvent to volume of
non-solvent selected for use as the formation medium, the larger in
length over a given period of time will the tubules and/or helices
which form from the lipid be. Conversely, the smaller in ratio of
volume of organic solvent to non-solvent selected, the shorter in
length will the selected lipid helices and/or tubules be. The lipid
is thus typically first dispersed in organic solvent and
non-solvent subsequently added thereto; and the volume ratio of
organic solvent to non-solvent, and the rate of addition of
non-solvent to organic solvent or vice versa, is predetermined so
as to predetermine a specific range of diameters and lengths (and
the medians of such ranges) of the lipid helices and/or tubules
which are formed in the solution. The concentration of the selected
lipid which is first dispersed in the selected organic solvent is
typically selected in the range of between about 0.3 mg/ml and
about 2.0 mg/ml. Once the lipid has been solvated in the selected
organic solvent, the preselected amount of non-solvent is added to
the lipid organic solvent solution or vice versa. Water, hexane or
the like acts as a poor or non-solvent with respect to the lipid
which, as a result of poor solvating effect on the lipid, causes
the lipid to self aggregate into a preselected tubular and/or
helical form depending on the predetermination of, inter alia, the
kind and amounts of organic solvent and non-solvent used as the
formation solution medium.
The most preferred organic solvents for use herein are relatively
polar organic solvents such as tetrahydrofuran, chloroform, and
alcohols and polyols, such as methanol, ethanol, propanol,
isopropanol, butanol, isobutanol, propylene glycol, ethylene glycol
and mixtures of two or more of all of the foregoing.
The inventive process herein typically yields tubules and/or
left-handed or right-handed helices having selected lengths of less
than about 1500 microns. A reaction mixture having helices and/or
tubules which fall within a pre-selected range of length, e.g.,
2-10, 2-20, 2-40, 5-20, 5-30, 5-50, 10-50, 10-100, 10-150, 10-300,
20-200, 30-100 and any desired similar restricted ranges having
preselected medians may be accomplished by varying one or more of:
(a) the time the lipid solution is allowed to sit shielded from
high energy radiation; (b) the ratio of volume of organic solvent
to non-solvent for use as a solvent medium; (c) the specific
organic solvent selected, (d) the temperature of the selected
solvent medium; (e) the concentration of surfactant used in the
organic solvent/non-solvent solution; and (f) the handedness of the
helical microstructures may be predetermined by preselecting the
chirality of the lipid with respect to a selected carbon atom, i.e.
preselecting a particular enantiomer.
Apart from a simple one-step addition of non-solvent to a
pre-prepared selected organic solvent lipid solution in a reaction
vessel, the non-solvent component of the formation solvent medium
may be added gradually over time to the pre-prepared solution of
the lipid in the selected organic solvent, such as by drop by drop
addition, dialysis or other gradual addition of the non-solvent to
the organic solvent solution over a relatively extended period of
time. Such prolongation of the period of time over which the
non-solvent component is added to the lipid solution, is another
variable which may be employed to select, predetermine and vary the
range in lengths (and medians thereof) of microstructures which may
be fabricated hereby. Such gradual additions may be accomplished in
a variety of conventional ways. For example a mixture of selected
lipid and organic solvent may be placed in dialysis tube or bag,
and the bag subsequently placed in a vessel containing water or to
which vessel water is gradually added for the purposes of allowing
the water to gradually invade the lipid/organic solvent mixture
over time through the dialysis bag.
The pre-prepared organic solvent lipid solution may alternatively
be added to the preselected amount of non-solvent in one step or
gradually over a preselected period of time in essentially the same
preselected manners that the non-solvent may be added to the
pre-prepared organic solvent lipid solution.
Although the inventive process herein may yield microstructures in
a selected formation solution whose lengths and diameters vary over
pre-selected ranges, formation solutions having microstructure
lengths which vary by as little as plus or minus about 5 microns in
standard deviation around a preselected median microstructure
length may be achieved. The typical range of standard deviations in
length around a preselected median length which may be achieved
herein by pre-selecting the kind and amounts of organic solvents,
temperature, concentration of lipid in solution and time of
allowing the lipid to self aggregate is from about 5 microns to
about 100 microns in standard deviation. The typical range of
standard deviations in diameter around a preselected median
diameter which is achievable herein is between about 0.05 and about
0.3 microns. Typically the standard deviation in tubule or helix
length around a preselected median length is less than about 60% of
the value of the preselected median length; and the standard
deviation in tubule or helix diameter around a preselected median
diameter is typically less than about 25% of the value of the
preselected median diameter. For example, if the preselected median
length of tubules yielded in a preselected formation solution is
about 170 microns, the solution will typically yield tubules having
lengths which range in standard deviation around the 170 micron
median by less than about 102 microns; similarly if the preselected
median diameter of helices yielded in a preselected solvent medium
is about 0.7 microns, the solution will typically yield helices
having diameters which range in standard deviation around 0.7
microns by less than abut 0.42 microns.
Following are some exemplary formation routines according to the
invention and the results thereof. In the following examples 1-12
the above referenced phospholipid II, where m and p were selected
as 8 and n and r were selected as 9, X and Y were selected as
methyl, and Z was selected as phosphoryl choline (DC.sub.23 PC, the
L-isomer thereof, or 1, 2-bis (10, 12-tricosadiynoyl)-
sn-glycero-3-phosphocholine) is selected for exemplary use:
EXAMPLE 1
0.5 mg of DC.sub.23 PC and 1 ml of ethanol is placed in a glass
vial. To the solution, 1.5 ml of distilled water is added and the
vial is covered and allowed to sit in the dark for about 10 hours
at room temperature. Upon addition of the water the solution turned
cloudy in minutes. After 10 hours the solution may be observed
under a Leitz Ortholux I optical microscope in both phase and dark
field. Tubules 1-20 microns long and 0.1-0.7 microns in diameter
are yielded.
EXAMPLE 2
0.5 mg of DC.sub.23 PC and 1 ml of ethanol are placed in a glass
vial. 1 ml of distilled water is added and the vial covered and
allowed to sit in the dark for about 10 hours at room temperature.
Viewing this solution in an optical microscope reveals tubules 1-40
microns long and 0.2-0.7 microns in diameter. Average tubule length
is about 11.9 microns with a standard deviation of plus or minus 6
microns.
EXAMPLE 3
4.0 mg of DC.sub.23 PC and 2.2 ml of ethanol are placed in a glass
vial. 1.8 ml of distilled water is added and the vial covered and
allowed to sit in the dark for about 10 hours at room temperature.
This solution yields tubules with an average length of about 23
microns with a standard deviation of plus or minus 11 microns and
with an average diameter of 0.47 microns and a standard deviation
of plus or minus 0.1 microns.
EXAMPLE 4
0.5 mg of DC.sub.23 PC and 1 ml of ethanol are placed in a glass
vial. 0.43 ml of distilled water is added and the vial covered and
allowed to sit in the dark for about 10 hours at room temperature.
This solution yields tubules 10-350 microns long and 0.2-3.0
microns in diameter with right-handed helical structures being
present having about the same dimensions as the tubules.
EXAMPLE 5
0.5 mg of DC.sub.23 PC and 1 ml of ethanol are placed in a glass
vial. 0.43 ml of distilled water are added and the vial covered and
allowed to sit for about 10 hours at room temperature. Irradiating
this solution at 4 degrees C in a Co.sup.60 source at a dosage of
9.2 megarads results in red microstructures. This solution yields
ruggedized tubules 10-300 microns in length. The solution yields
tubules having diameters of 0.73 .+-.0.1 microns and also contains
right-handed helical structures of about the same dimensions.
EXAMPLE 6
0.7 mg of DC.sub.23 PC and 0.7 ml of ethanol are placed in a vial.
0.3 ml of distilled water is added and the vial covered and allowed
to sit in the dark for about 144 hours. The solution yields tubules
having an average length of about 50 microns with a standard
deviation of plus or minus 31 microns, and right-handed helices are
also yielded.
EXAMPLE 7 0.5 mg of DC.sub.23 PC and 0.75 ml of ethanol are placed
in a glass vial. 0.25 ml of distilled water is added and the vial
covered and allowed to sit in the dark for about 360 hours at room
temperature. This solution yields tubules 30-1200 microns in length
with diameters varying from 0.5-3.0 microns. The tubules have an
average length of about 170 microns plus or minus 92 microns and an
average diameter of about 0.73 microns plus or minus 0.1 microns.
The solution also contains right-handed helical structures of about
the same dimensions. The diameter of a single tubule may also vary
with one end being 0.5 microns and the other as large as 3
microns.
EXAMPLE 8
0.5 mg of DC.sub.23 PC and 0.5 ml of isopropanol is placed in a
glass vial. 0.5 ml of distilled water is added and the vial covered
and allowed to sit in the dark for about 10 hours at room
temperature. The solution yields tubules 10-170 microns in length,
0.2-1.0 microns in diameter and also yields right-handed helical
structures.
EXAMPLE 9
The microstructures may also be fabricated by, slowly adding water
over time to an organic solvent lipid solution. For example, in a
dialysis tube, 0.5 mg of DC.sub.23 PC is added to 1.5 ml of
ethanol. The bag is then placed in a beaker of 4 liter total
capacity containing 500 ml of 95% ethanol. Water is added to the
beaker drop by drop at a rate of 88 ml/hour until there is a total
volume in the beaker of 2 liter. All of the solutions are
maintained at room temperature. The bag is then removed from the
beaker and placed in a beaker with 1 liter of distilled water and
dialyzed at room temperature for 3 hours. The tubules are then
removed from the bag and placed in a glass vial and lowered in
temperature to 4 degrees C and polymerized by gamma radiation in a
Co.sup.60 source The tubules yielded from this preparation range in
lengths from 10-350 microns and an average diameter of 0.7 microns
and right-handed helical structures are also yielded. No change in
the structures occurs during polymerization.
EXAMPLE 10
1.0 mg of DC.sub.23 PC and 0.4 ml of chloroform with a trace amount
of water is added to a glass vial; 3.6 ml of hexane is then added
to the vial; the vial is covered and stored in the dark for about
10 hours at room temperature. This solution yields tubules from
less than a micron in length up to 10 microns in length.
EXAMPLE 11
0.3 mg of DC.sub.23 PC and 0.9 ml of propylene glycol are added to
a glass vial, and 0.1 ml of distilled water is next added to the
vial. The vial is covered and allowed to sit in the dark for about
10 hours at room temperature. This solution yields short tubules no
longer than about 10 microns in length.
EXAMPLE 12 30.04 mg of DC.sub.23 PC and 29.95 ml of ethanol are
placed in a glass vial. 12.96 ml of distilled water is next added
and allowed to sit at room temperature for about 264 hours. This
solution yields tubules 10-350 microns long and 0.2-3.0 microns in
diameter; right-handed helical structures are also yielded.
EXAMPLE 13
1.17 mg of 1,2-bis (10, 12-tricosa diynoyl,
22-ene)-sn-glycero-3-phosphocholine and 1.17 ml of ethanol are
placed in a glass vial. The solution is then cooled to 5.0.degree.
C. .+-.0.7.degree. C. and 1.17 ml of distilled water at 5.0.degree.
C. is added to the vial. The vial is kept at 5.0.degree. C. for two
weeks and the solution is dialyzed to distilled water. The solution
yields tubules 2-40 microns in length and right-handed helical
microstructures are also yielded.
EXAMPLE 14
2.42 mg of 2, 3-bis (10,12-tricosa
diynoyl)-sn-glycero-1-phosphocholine, the D isomer of DC.sub.23 PC,
and 2.42 ml of isopropanol is placed in a glass vial. To this
solution 2.42 ml of distilled water is added and allowed to sit for
10 hours. The solution yields tubules 5-200 microns in length and
left-handed helical microstructures are also yielded.
It will now be apparent to those skilled in the art that other
embodiments, improvements, details, and uses can be made consistent
with the letter and spirit of the foregoing disclosure and within
the scope of this patent, which is limited only by the following
claims, construed in accordance with the patent law, including the
doctrine of equivalents.
* * * * *